Authors: David M.G. Halpin, Mark T. Dransfield, MeiLan K. Han, C. Elaine Jones, Sally Kilbride, Peter Lange, David A. Lipson, David A. Lomas, Fernando J. Martinez, Steve Pascoe, Dave Singh, Robert Wise, Gerard J. Criner
Published: 2020-04-16
DOI: 10.1183/13993003.01921-2019
Source: Full article
IMPACT, a 52-week, randomised, double-blind trial, assessed the efficacy and safety of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapyversusFF/VI or UMEC/VI in patients with symptomatic COPD and a history of exacerbations.Subgroup analyses assessed whether the efficacy of FF/UMEC/VIversusFF/VI or UMEC/VI and UMEC/VIversusFF/VI varies according to prior exacerbation history, and the combined effects of exacerbation history and blood eosinophil counts. Three subgroups were defined: single moderate (1 moderate/no severe; n=3056 (30%)), frequent moderate (≥2 moderate/no severe; n=4628 (45%)) and severe (≥1 severe/any moderate; n=2671 (26%)). End-points included annual on-treatment moderate/severe exacerbation rate (pre-specified), lung function and health status (both post-hoc).Moderate/severe exacerbation rates (reduction % (95% CI)) were reduced in the FF/UMEC/VI groupversusFF/VI (single moderate 20% (10–29), frequent moderate 11% (2–19), severe 17% (7–26)) andversusUMEC/VI (single moderate 18% (5–29), frequent moderate 29% (21–37), severe 26% (14–35)). Moderate/severe exacerbation rates were reduced in the FF/VI groupversusUMEC/VI in the frequent moderate subgroup; a numerical reduction was observed in the severe subgroup (single moderate 2% (−12–18), frequent moderate 21% (11–29), severe 11% (−3–22)). Moderate/severe exacerbation rates were lower in the FF/VI group compared with UMEC/VI in patients with higher eosinophil counts. FF/UMEC/VI improved lung function and health statusversusboth dual therapies irrespective of exacerbation subgroup. UMEC/VI improved lung functionversusFF/VI in all subgroups.Triple therapy was more effective than dual regardless of exacerbation history, consistent with results in the intent-to-treat population. Comparisons between dual therapies were influenced by prior exacerbation history and eosinophil counts.